IMMUNOLOGY2024™ Conference Recordings-Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism

Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism

Video Transcription

Video Summary

The talk focused on exhausted CD8 T cells in tumors and how they survive despite harsh metabolic conditions. Using RNA-seq, the speaker identified the monocarboxylate transporter SLC16A11/MCT11 as highly enriched in terminally exhausted T cells. MCT11 enabled these cells to take up and oxidize lactate. Deleting or blocking MCT11 reduced lactate use, improved cytokine production, and lowered exhaustion marker levels per cell without preventing exhaustion differentiation. Antibody treatment against MCT11 also reduced tumor burden and cleared some tumors in mice. Overall, MCT11 supports exhausted T cell metabolism and may be a promising immunotherapy target.

Keywords

CD8 T cells

tumor exhaustion

SLC16A11 MCT11

lactate metabolism

immunotherapy target